Ultrasonography as a sensitive and specific diagnostic modality for the detection of ectopic ureters in urinary incontinent dogs

Abstract Ultrasonography is a widely available diagnostic modality for the identification of dogs with suspected ureteral ectopia; however published studies detailing its sensitivity and specificity are currently lacking. The aim of this retrospective, descriptive, diagnostic accuracy study was to evaluate the sensitivity and specificity of ultrasonography for the diagnosis of ureteral ectopia in incontinent dogs presenting to a referral institution, using cystoscopy as the gold standard. Medical records of urinary incontinent dogs presenting to a single institution (n = 38) were retrospectively reviewed for the presence of ureteric insertion abnormalities and concurrent urinary tract abnormalities. Ultrasonographic findings were compared with those from cystoscopic examination to determine diagnostic accuracy. The relationship between the presence of concurrent urinary tract abnormalities and ureteral ectopia was assessed using an independent samples t‐test and Mann–Whitney test. Statistical significance was set at P ≤ 0.05. Ultrasonography had a sensitivity of 93.5%, specificity of 100%, and diagnostic accuracy of 95% when identifying dogs with ureteral ectopia. When classifying individual ureters as ectopic or non‐ectopic, sensitivity was 87.8% and specificity was 86.7%. Dogs with ureteral ectopia had significantly more concurrent urinary tract abnormalities on ultrasound than unaffected dogs (P = 0.004). Ectopic ureters were associated with significantly more concurrent ipsilateral upper urinary tract ultrasonographic abnormalities than unaffected ureters (P < 0.001). Ultrasonography performed by an experienced ultrasonographer is a sensitive and specific screening tool for canine ureteral ectopia, which eliminates the need for heavy sedation, general anesthesia, and advanced imaging, although it should not be relied upon as the sole diagnostic modality for the assessment of individual ureters.


INTRODUCTION
Ureteral ectopia is the most common cause of urinary incontinence in juvenile dogs. 1 It is a congenital abnormality in which one or both ureteral orifices are inappropriately located distal to the bladder trigone. Intramural and extramural ectopic ureters (EUs) have been reported in dogs, with >95% of cases being intramural. [2][3][4] Female dogs are often more severely urinary incontinent and are over-represented in dogs presenting with urinary incontinence secondary to ureteral ectopia, which has been theorized to be due to their shorter urethral length. 3,5 It is currently hypothesized that there is a genetic basis for this condition with Labrador Retriever, Golden Retriever, Newfoundland, Siberian Husky , Poodle, soft-coated Wheaten Terrier, West Highland White Terrier, and Skye Terrier breeds being predisposed. 1,3,5,6 Ureteral ectopia is usually suspected based on clinical history, signalment, and physical examination findings. Diagnostic imaging is then utilized to evaluate the path of the distal ureter, identify the ureteral orifice, and to identify concurrent abnormalities such as hydroureter and hydronephrosis.
Historically, radiographic excretory urography combined with retrograde urethrocystography has been relied upon to identify EUs or associated pathology. 2,[7][8][9] Excretory urography has been reported to identify the location of ectopic ureteral orifices correctly in 66-78.2% of cases, 2,7,8 with fluoroscopy and evacuation of rectal contents shown to improve sensitivity. 10 More recently, CT excretory urography (CT) and four-dimensional CT excretory urography (4D-CTEU) have been used for the diagnosis of EUs with a reported 73-100% and 97% sensitivity, respectively. 10,11,12 With the advancement of endoscopic technology, cystoscopy has been described as the gold standard for EU diagnosis as it allows the operator to visualize the ureteral orifices directly, with a reported sensitivity of 100%, as well as enabling concurrent laser ablation of intramural EUs. 5,8,10 One of the limitations of excretory urography, CT, and cystoscopy is the requirement for general anesthesia or heavy sedation. Intravenous administration of iodine-based contrast medium for excretory urography and CT is associated with a low risk of adverse reactions and acute kidney injury. 13 Abdominal ultrasonography (AUS) can provide a detailed assessment of the upper urinary tract and the position of the ureters, without the need for general anesthesia (and in some cases without sedation) or intravenous contrast injection. 5 While its use has been recommended alongside cystoscopy, there is limited information on the sensitivity or specificity of this imaging modality in dogs with ureteral ectopia. Lamb  The primary aim of the current study was to evaluate the sensitivity and specificity of AUS for diagnosis of ureteral ectopia in dogs with urinary incontinence presenting to a referral institution, using cystoscopic findings as the gold standard for comparison. We hypothesized that AUS would have a sensitivity >85% for a diagnosis of EU when compared to cystoscopy and therefore would be a useful imaging modality in clinical cases. The secondary aim was to assess whether any other AUS findings could be used to aid the diagnosis of ureteral ectopia.

Data recording and analysis
Medical records were reviewed by a small animal veterinary intern (O.T.). Recorded data included the following: signalment, presenting complaint(s), AUS findings, and cystoscopy findings. Reports of AUS performed by a European College of Veterinary Diagnostic and Imaging (ECVDI)-certified veterinary radiologist, or a radiology resident under the supervision of an ECVDI-certified veterinary radiologist, were reviewed and urinary tract abnormalities were recorded (Tables 1 and 2). The presence of ureteral ectopia was documented.
Within the AUS report, each ureter was classified as either intramural ectopic, extramural ectopic, or normal. The dog was then categorized as either "positive for ureteral ectopia" or "negative for ureteral ectopia" based on AUS. All concurrent urinary tract abnormalities (CUTA) included within the radiologist's report were recorded. The CUTA specifically affecting the ipsilateral kidney or ureter were subclassified as concurrent ipsilateral upper urinary tract abnormalities (CIUTA).
Ureteral and renal pelvis diameters included within the radiologist report were recorded. The reports from the cystoscopic examination performed by a board-certified surgeon for each dog were reviewed and each ureter was classified as either ectopic or non-ectopic. The dog was then categorized as either "positive for ureteral ectopia" or "negative for ureteral ectopia." For cases with incomplete medical records, AUS images were retrieved and measurements were performed by a small animal     Table 1).

DISCUSSION
This study aimed to evaluate the sensitivity and specificity of AUS for the diagnosis of ureteral ectopia in dogs presenting to a referral institution with urinary incontinence and to assess whether any other AUS findings could be used to aid the diagnosis of ureteral ectopia. A sensitivity of 87.8% was observed when AUS was utilized to identify the presence of an EU when assessing individual ureters, which increased to 93.5% when utilized to determine the presence of ureteral ectopia for each dog, leading us to accept our hypothesis. This is similar to the previously reported sensitivity of 91% for AUS diagnosis of ureteral ectopia when compared to contrast radiography. 14 The AUS sensitivity reported in this study is similar to that of CT, lower than that of 4D-CTEU, and greater than that of intravenous urography. 10,12 The specificity of AUS for EU has not been previously reported. AUS has the benefit that it allows the thorough evaluation of the abdominal viscera, urinary tract, and concurrent abnormalities associated with ureteral ectopia without the requirement for a general anesthetic/heavy sedation or the administration of intravenous contrast agents.
Cystoscopic examination findings were used as the gold standard for comparison with AUS in this study, due to the previously reported 100% sensitivity of this technique. 8 Previous studies have suggested that female dogs are more likely to present with EUs, which is consistent with the findings reported here, as 97% (30/31) of the dogs diagnosed with EUs were female.
Of the dogs that were diagnosed with ureteral ectopia, 71% (22/31) were Golden retrievers and 10% (3/31) were Labradors. The overrepresentation of Golden retrievers is not unexpected as the literature suggests they are a predisposed breed, 18,19 however, the population of dogs investigated for urinary incontinence at the QVSH may also be skewed due to other ongoing research involving Golden retrievers.
A total of 12 dogs (32%) were diagnosed with bilateral EUs which is consistent with the previously reported prevalence of 32-64% in EU populations. 11,17,19 Extramural EUs are reported to be rare in dogs 18 and all 43 EUs diagnosed in this study were intramural, with the only suspected extramural ectopic ureter identified to be non-ectopic during the cystoscopic examination. Cystoscopic classification of ectopic ureters as either intramural or extramural has not been described in the literature and classification was reliant on the operator's assessment of the ureter's morphological features. All ectopic ureters were subsequently successfully laser-ablated confirming the suspicion of an intramural phenotype.
Ultrasound diagnosis of EUs involves the identification of a ureteral jet by doppler, the identification of the tubular ureteral structure distal to the bladder neck, and the presence of secondary hydroureter. 14 Intravenous administration of furosemide (0.5 mg/kg) has been reported to aid the location of the ureteral orifice in "normal" dogs. 20 Medical records indicate that at least 1 dog in this study received intravenous furosemide, although the number of dogs that received diuretic is difficult to ascertain as it was inconsistently documented. It may be useful for future studies to assess whether the administration of intravenous furosemide affects the diagnostic accuracy of AUS for identification of EUs.
No extramural EUs were diagnosed by cystoscopy in this study, so the sensitivity and specificity of AUS for the identification of extramural EU was not assessed.
There are limitations regarding the use of AUS as the primary diagnostic imaging modality to diagnose and identify EUs in dogs. The most significant is that AUS is a highly operator-dependent modality and there is a high level of skill required to consistently acquire diagnostic quality images of a mobile, soft tissue tract such as a ureter. Image acquisition is made more complicated by the presence of other congenital abnormalities, such as a short urethra, lack of a distinct bladder neck, or an intrapelvic bladder. 18 These abnormalities can make it difficult to perform complete urethral evaluation due to the acoustic shadowing associated with the pelvis. In this study, AUS incorrectly identified one normal ureter as an extramural ectopic ureter. The AUS report described a tubular structure running parallel to the bladder neck and proximal urethra, leading to the assumption that the ureter was extra- mural. An explanation for this misdiagnosis could be that a blood vessel may have been mis-identified as a ureter. Even once a ureter is located, there can be difficulties in identifying which ureter is being assessed as the image acquisition in AUS is continuous. One of the dogs in this population was correctly diagnosed with unilateral EU, but the operator was unable to determine which kidney the ureter was associated with. In this case, the lack of identification of the affected side did not ultimately change the treatment plan. Limitations of this study include its retrospective nature and the relatively small study population, which is inherent to the relative rarity of ureteral ectopia and cases referred for investigation of urinary incontinence. As a referral institution, the cases that present to the QVSH have often undergone preliminary investigations and medical treatment trials which may have ruled out common causes of urinary incontinence other than ureteral ectopia, such as urethral sphincter mechanism incompetence, bacterial cystitis, or cystolithiasis. This results in a higher prevalence of ureteral ectopia in the study population than the population presenting to the general practitioner.
As an imaging modality, AUS is highly operator dependent and features such as corticomedullary distinction are highly subjective, which means that the results presented here cannot necessarily be extrapolated to other institutions. Due to the retrospective nature of the study, the surgeon who operated the cystoscopy was not blinded to the findings of the AUS. There is a level of subjectivity when identifying ectopic ureters in dogs with a poorly defined bladder neck and the lack of blinding could have resulted in a potential bias when determining whether a ureter with an opening at the distal aspect of the bladder neck is ectopic. A prospective study with the appropriate blinding is recommended to confirm the findings of this study. In conclusion, AUS is a specific and sensitive initial screening tool for EU diagnosis in dogs with urinary incontinence. In cases where the cost, speed, and risk of the diagnostic technique is a concern, AUS can be used as an alternative to CT as a screening tool and can achieve a higher sensitivity to intravenous excretory urography for identifying intramural EU in dogs. If the ureteral orifice cannot be identified clearly on AUS, diagnosis, and identification of EU in urinary incontinent dogs may be aided by assessing the presence of CUTA and number of CIUTA but further investigation is necessary to characterize this relationship fully.

ACKNOWLEDGMENTS
The authors would like to thank Professor Michael Herrtage for his assistance in performing and supervising a significant proportion of the abdominal ultrasonographic examinations included in this study.